Potential roles of hsacirc₀₀₀₃₀₉₈ and hsacirc₀₀₁₃₉₅₈ in pathophysiology of renal cell carcinoma

Abstract

Background: Renal cell carcinoma (RCC) is the predominant form of kidney cancer with certain subtypes carrying a relatively poor prognosis. Circular RNAs (circRNAs) have recently emerged as promising tools for early diagnosis of the more malignant subtypes in the context of competing endogenous RNA (ceRNA) networks. Materials and methods: This is an experimental and in-silico study of the expression of hsacirc₀₀₀₃₀₉₈ and hsacirc₀₀₁₃₉₅₈ and their interaction with associated miRNAs and mRNAs in the context of tumor versus healthy tissues in RCC. The expression was assessed using qRT-PCR and ceRNA network was constructed using CircInteractome, miRTargetlink2, TargetScan, miRWallk, and STRING databases. GEPIA was employed for survival analysis and Cytoscape was used for network analysis. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the clinical and diagnostic value of hsacirc₀₀₀₃₀₉₈ and hsacirc0013958. Results: Both hsacirc₀₀₀₃₀₉₈ and hsacirc₀₀₁₃₉₅₈ were expressed at significantly lower levels in tumor tissues compared with normal tissues (P-value =0.013, < 0.001). Interestingly, there was a significant association between the expression of hsacirc₀₀₁₃₉₅₈ and kidney disease and tumor type. In silico analysis of the ceRNA network identified mRNAs and miRNAs crucial for RCC. Survival analysis of hub genes linked to each circRNA revealed several genes significantly impacting patient survival. Besides, hsacirc₀₀₀₃₀₉₈ and hsacirc₀₀₁₃₉₅₈ could act as diagnostic markers in RCC. Conclusion: Our research showed that hsacirc₀₀₀₃₀₉₈ and hsacirc₀₀₁₃₉₅₈ were significantly downregulated in RCC tumors. This dysregulation of their miRNA/mRNA network affected important carcinogenic processes such as adhesion, migration, signaling, and cell cycle, which in turn provided insights into the molecular mechanisms of RCC.